Biological processes appear in many different industrial settings. For example, fermentation processes pervade the biofuels, pharmaceutical, biotechnology, food, and beverage industries. Wastewater treatment is yet another industrial setting where microbiological processes play an important role.
The key performance indicators of industrial bioprocesses, such as final product concentration, process efficiency, and yield, are heavily influenced by the metabolic rates of cellular populations throughout the industrial process (e.g., fermentation and wastewater treatment). In the majority of industrial bioprocesses, however, only environmental parameters, such as temperature and pH, are monitored due to the lack of a simple and rapid way to measure the metabolic activities that are directly responsible for creating the desired product. As a result, most processes are operated without adequate information about the physiological state of biological catalysts used in the process.
Correctly managing cellular populations is generally recognized to be one of the most challenging components of an industrial process or bioprocess. Inconsistent or inaccurate management practices negatively impact the consistency and efficiency of the process. However, the standard method of cellular population analysis by methods such as light microscopy and viability staining presents numerous difficulties and limitations in an industrial production setting. Such difficulties include the inherent variability in results collected by different people due to factors such as the subjective nature of discriminating cells from non-living particles and classifying cells as either alive or dead based on a colored stain applied to the cells. Yet another limitation is that the microscopy method has only two levels for classifying cells: alive or dead. This binary system fails to capture the biological reality that cells exist along a continuous scale from alive to dead and their exact position along this continuum is determined by a multitude of factors.
Numerous examples of methods for quantifying cell concentrations can be found in the prior art. For example, U.S. Pat. Nos. 5,445,946 and 7,527,924 disclose methods and/or devices for cell quandification using fluorescence. U.S. Patent Application Publication 2004/0157211 discloses methods and/or devices for cell quandification using digital microscopy. The major shortcoming of these inventions is that they provide only alternative means of quandifying cellular populations, and not a means of measuring the metabolic rates of cellular populations. To measure metabolic rates, it has historically been necessary to use a method of quandifying the production carbon dioxide and/or consumption of oxygen by cellular populations using instruments such as a respirometer, manometer, or fermontagraph, (See e.g., Water Sci Technol. 2007; 55(10):1-9. “Respirometric assessment of biodegradation characteristics of the scientific pitfalls of wastewaters.”). Such instruments, however, are difficult to operate and maintain partially due to the complexities of measuring gasses, which are heavily influenced by temperature, pressure, and interactions with other matter.
There thus exists an ongoing need for improved methods of analyzing cellular populations in industrial settings. In particular, there is a need for methods and systems capable of determining metabolic rates of cellular populations, as opposed to concentration of the cellular populations, while also reducing the inherent variability and difficulties associated with current practices of managing cellular populations in industrial processes.